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Background and Importance Empirical antibiotic therapy plays a decisive role in the management of sepsis, where early and appropriate treatment is directly related to patient outcomes.Aim and Objectives The aim of this study was to evaluate whether the adequacy of empirical therapy initiated in the emergency department (ED) influences hospital mortality and the need for admission to the intensive care unit (ICU). Secondary objectives included analysing the length of hospital stay and the impact of therapy adjustment after microbiological results became available.Material and Methods We conducted a retrospective observational study including patients diagnosed with sepsis in the ED between January and December 2024. Demographic data, source of infection, adequacy of initial empirical antibiotic therapy according to national and local guidelines, microbiological findings, and subsequent therapeutic adjustments were collected. Patients starting targeted therapy from the outset were excluded.Primary outcomes were hospital mortality and ICU admission. The secondary outcome was hospital length of stay. Statistical analyses were performed using Chi-square tests for categorical variables and Mann–Whitney U tests for continuous variables.Results A total of 51 patients were included, of whom 26 (51.0%) received appropriate empirical therapy.Overall hospital mortality was 19.6% (10/51). Mortality was significantly lower in the group with appropriate empirical therapy (3.9%, 1/26) compared with those receiving inappropriate therapy (36.0%, 9/25; p=0.001; OR 0.07; 95% CI 0.01–0.41).ICU admission was required in 3 patients (5.9%), of whom 2 (66.7%) had received inappropriate empirical therapy. Differences were not statistically significant (p=1.00).Median length of stay was 6 days in both groups (p=0.66).After excluding patients with initially adequate empirical therapy, 36 cases were analysed. Antibiotic treatment was modified in 13 (36.1%), showing lower mortality (7.7% vs 52.2%) compared with non-adjusted patients (p=0.21; OR 0.19; 95% CI 0.02–1.76).Conclusion and Relevance In this cohort, appropriate empirical antibiotic therapy in the ED was associated with significantly lower hospital mortality in patients with sepsis. No significant differences were observed in ICU admission or hospital stay, likely due to the small number of events. Adjustment of therapy after microbiological confirmation showed a trend towards improved survival. These findings highlight the importance of optimising empirical antibiotic selection in the ED and reassessing adequacy once microbiological results are available.Conflict of Interest No conflict of interest